The specific objectives of the proposed research are elucidation of the metabolism of retinoic acid and determination of the biological significance of retinoic acid metabolism. This project will be approached by four avenues of investigation: determination of target-tissue metabolite profiles by high-pressure liquid chromatography; measurement of the biological activity of the metabolites in at least two vitamin A-responsive test systems; determination of the tissues responsible for metabolism of retinoic acid via in vitro experiments; and isolation and identification of the target-tissue metabolites. We hope to pinpoint metabolites which may be obligatory for the systemic functions of vitamin A, namely maintenance of growth, reproduction, bone remodeling and epithelial differentiation. In addition, the results of the bioassay experiments will provide valuable information about the anticarcinogenic activity of retinoic acid metabolites